The Pathological Mechanisms and Therapeutic Molecular Targets in Arteriovenous Fistula Dysfunction.

The number of patients with end-stage renal disease (ESRD) requiring hemodialysis is increasing worldwide. Although arteriovenous fistula (AVF) is the best and most important vascular access (VA) for hemodialysis, its primary maturation failure rate is as high as 60%, which seriously endangers the prognosis of hemodialysis patients. After AVF establishment, the venous outflow tract undergoes hemodynamic changes, which are translated into intracellular signaling pathway cascades, resulting in an outward and inward remodeling of the vessel wall.

Rhodojaponin VI ameliorates podocyte injury related with MDM2/Notch1 pathway in rat experimental membranous nephropathy.

Aim: Rhodojaponin VI (R-VI) is the key compound of Rhododendron molle G. Don (Ericaceae) (RM) with effective clinical application in rheumatoid arthritis and chronic glomerulonephritis. In our study, we tried to explore the effect of R-VI on the rat model of membranous nephropathy.

MDM2 accelerated renal senescence via ubiquitination and degradation of HDAC1.

Senescence, an intricate and inevitable biological process, characterized by the gradual loss of homeostasis and declining organ functions. The pathological features of cellular senescence, including cell cycle arrest, metabolic disruptions, and the emergence of senescence-associated secretory phenotypes (SASP), collectively contribute to the intricate and multifaceted nature of senescence. Beyond its classical interaction with p53, murine double minute gene 2 (MDM2), traditionally known as an E3 ubiquitin ligase involved in protein degradation, plays a pivotal role in cellular processes governing senescence.

Early growth response protein 2 promotes partial epithelial-mesenchymal transition by phosphorylating Smad3 during renal fibrosis.

Chronic kidney disease (CKD) is a serious health problem worldwide, which ultimately leads to end-stage renal disease (ESRD). Renal fibrosis is the common pathway and major pathological manifestation for various CKD proceeding to ESRD. However, the underlying mechanisms and effective therapies are still ambiguous.

GRK5 promoted renal fibrosis via HDAC5/Smad3 signaling pathway.

Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD), poses a significant burden in the aging population, and is a major cause of end-stage renal disease (ESRD). In this study, we investigated the role of G protein-coupled receptor kinases (GRKs) 5 in the pathogenesis of renal fibrosis. GRK5 is a serine/threonine kinase that regulates G protein-coupled receptor (GPCR) signaling.

Minichromosome maintenance 6 protects against renal fibrogenesis by regulating DUSP6-mediated ERK/GSK-3β/Snail1 signaling.

Minichromosome maintenance 6 (MCM6) has been implicated in the progression of various malignant tumors; however, its exact physiological function in kidney diseases remains unclear. Here, we demonstrated that MCM6 levels showed a significant increase in the proximal tubular cells during progressive renal fibrosis in two unrelated fibrotic models, including unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI). Depletion of MCM6 aggravated partial epithelial-mesenchymal transition, extracellular matrix accumulation, and myofibroblast activation in the kidneys of UUO or UIRI mice.

UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability.

Background: Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is gradually deepening, the diagnosis and treatment methods are still very lacking. Uncoupling protein 1 (UCP1) is a nuclear encoded protein in mitochondria inner membrane and plays an important role in regulating energy metabolism and mitochondrial homeostasis.

Cell-Cycle Dysregulation in the Pathogenesis of Diabetic Kidney Disease: An Update.

In the last few decades, the prevalence of diabetes mellitus (DM) has increased rapidly. Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD) globally, attributed to hemodynamic changes and chronic hyperglycemia. Recent findings have emphasized the role of cell-cycle dysregulation in renal fibrosis and ESRD.

MULT1-Encoding DNA Alleviates Schistosomiasis-Associated Hepatic Fibrosis via Modulating Cellular Immune Response.

Purpose: In schistosomiasis-associated hepatic fibrosis, the role of murine UL16-binding protein-like transcript 1 (MULT1), the strongest ligand of natural killer group 2-member D receptor (NKG2D), remains unclear. Here, -infected mice administered with MULT1-encoding DNA were used to test MULT1 as a potential therapy for schistosomiasis-associated hepatic fibrosis and explore relevant mechanisms.

Materials And Methods: A recombinant plasmid encoding MULT1 (p-rMULT1) was constructed and administered to -infected BALB/c mice via hydrodynamic tail vein injection.

Selenium Status and Its Antioxidant Role in Metabolic Diseases.

Selenium (Se), in the form of selenoproteins, is an essential micronutrient that plays an important role in human health and disease. To date, there are at least 25 selenoproteins in humans involved in a wide variety of biological functions, including mammalian development, metabolic progress, inflammation response, chemoprotective properties, and most notably, oxidoreductase functions. In recent years, numerous studies have reported that low Se levels are associated with increased risk, poor outcome, and mortality of metabolic disorders, mainly related to the limited antioxidant defense resulting from Se deficiency.

Modes of podocyte death in diabetic kidney disease: an update.

Diabetic kidney disease (DKD) accounts for a large proportion of end-stage renal diseases that require renal replacement therapies including dialysis and transplantation. Therefore, it is critical to understand the occurrence and development of DKD. Podocytes are mainly injured during the development of DKD, ultimately leading to their extensive death and loss.

Effects and mechanisms of probucol on aging-related hippocampus-dependent cognitive impairment.

Background: In the present study, we aimed to investigate the effects of probucol on aging-related hippocampus-dependent cognitive impairment and explore the potential mechanisms.

Methods: D-galactose (100 mg/kg, once daily for 6 weeks) was subcutaneously injected to induce aging in mice. Then the mice were administered with probucol or vehicle once a day for 2 weeks.

Inhibition of MAD2B alleviates venous neointimal formation by suppressing VSMCs proliferation and migration.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential events in venous neointimal hyperplasia (VNH), a culprit of arteriovenous fistula (AVF) malfunction. Mitotic arrest-deficient protein 2B (MAD2B) is a critical regulator of cell proliferation and differentiation in many scenarios. To address the role of MAD2B in VSMCs proliferation and migration during VNH, AVFs from patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) mice were used to evaluate MAD2B expression.

The Role of CXCL12 in Kidney Diseases: A Friend or Foe?

Background: Chemokines are a family of proteins mainly mediating the homing and migration of various cells. The CXC chemokine CXCL12 is a member of low-weight-molecular chemokines. In the kidney, CXCL12 is pivotal for renal development and exerts a modulatory effect in kidney diseases under different etiologic settings by binding with CXC chemokine receptor 4 (CXCR4) or CXC chemokine receptor 7 (CXCR7).

Relieving lipid accumulation through UCP1 suppresses the progression of acute kidney injury by promoting the AMPK/ULK1/autophagy pathway.

Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression, and poor prognosis. Recent evidence suggests that AKI is accompanied by significant metabolic abnormalities, including alterations in lipid metabolism. However, the specific changes in lipids in AKI, and their role and regulation mechanisms are currently unclear.

Mechanism and application of metformin in kidney diseases: An update.

Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5' Adenosine monophosphate-activated Protein Kinase (AMPK). Beyond the anti-diabetic effect, accumulative pieces of evidence have revealed that metformin also everts a beneficial effect in diverse kidney diseases. In various acute kidney diseases (AKI) animal models, metformin protects renal tubular cells from inflammation, apoptosis, reactive oxygen stress (ROS), endoplasmic reticulum (ER) stress, epithelial-mesenchymal transition (EMT) via AMPK activation.

Oxidative Stress and Renal Fibrosis: Mechanisms and Therapies.

Oxidative stress results from the disruption of the redox system marked by a notable overproduction of reactive oxygen species. There are four major sources of reactive oxygen species, including NADPH oxidases, mitochondria, nitric oxide synthases, and xanthine oxidases. It is well known that renal abnormalities trigger the production of reactive oxygen species by diverse mechanisms under various pathologic stimuli, such as acute kidney injury, chronic kidney disease, nephrotic syndrome, and metabolic disturbances.